In recent years there has been increased awareness and concern about the ?epidemic of loneliness? among older adults and other general population, but the prevalence is even higher among people with schizophrenia. Loneliness is a significant risk factor for medical comorbidity, cognitive dysfunction, reduced functional capacity, lower well-being, and earlier mortality. The mortality risk associated with loneliness is double that for obesity, and equivalent to smoking 15 cigarettes per day. Notably, many of the deleterious effects associated with loneliness parallel those associated with schizophrenia and aging. This convergence raises a question of whether loneliness significantly contributes to the deficits in health, cognition and functional capacity, physiologic function, and well-being among middle-aged and older adults with schizophrenia. The proposed project is the first comprehensive study of the nature, longitudinal stability, and deleterious impact of loneliness in schizophrenia. Given recent conceptualizations of schizophrenia as a systemic disorder resulting in accelerated aging, and the manner in which loneliness may evolve over the life-course, the focus for this study will be on the effects of loneliness with age among middle-aged and older adults with schizophrenia (n=120) as well as age-comparable non-psychiatric comparison (NC) subjects (n=90). The study employs a longitudinal burst design, with in-person visits and assessments of key variables at baseline, 6-, and 12-months. For seven days following each of the three primary study visits, smartphone-based Ecological Momentary Assessment (EMA) will be used to measure loneliness, social activity, and mood in real-time. Our primary aims include determining the associations of schizophrenia and aging with persistent loneliness, and the degree to which the associations are independent of social isolation and depressive symptoms. The other primary aim is to determine the association of persistent loneliness over 6- and 12-months with levels and patterns of biological markers of health, medical comorbidity, cognitive dysfunction, functional capacity, and health-related quality of life. Hypotheses predict schizophrenia being associated with worse and more persistent loneliness, and that persistent loneliness will be associated with worse biological markers of health and other outcomes. We also expect these associations to increase with advancing age. Stability and temporal relationships between acute loneliness, social activity, and mood measured in real-time using EMA, and associations of these patterns with those from the standard in-person measures will also be assessed. The data from this project will fill a critical unmet need for empirical data to guide the content and focus of efforts to prevent and reduce deleterious biological and longer-term health outcomes and diminished well-being in older adults with schizophrenia. Together, this study represents a significant and innovative step in furthering efforts toward more effective, comprehensive, individualized prevention and treatment of loneliness and its adverse effects in middle-aged and older adults with schizophrenia.